Highlights of CEGIR Publications

Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR)
- Characterizing Variants of Eosinophilic Esophagitis
- Exploring Risk Factors for SARS-CoV-2 in Children with Asthma and Allergy
- Updating Terminology for Eosinophilic Gastrointestinal Diseases

Validation of self-reported diagnosis of eosinophilic gastrointestinal disorders patients enrolled in the CEGIR contact registry
Clin Res Hepatol Gastroenterol. Available online 5 November 2020.

In a letter to the editor published in Clinics and Research in Hepatology and Gastroenterology, researchers describe their work to validate the information of patient-reported data supplied to a contact registry established by the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR), with support from the Data Management Coordinating Center of the Rare Diseases Clinical Research Network.

The purpose of the research was to validate the information that patients supplied to the registry regarding diagnoses, procedures, and symptoms of eosinophilic gastrointestinal diseases (EGID) by comparing it to what their physicians reported, and to lab reports.

Among the findings, researchers observed:

100% agreement between the participant- and physician-reported diagnosis of EGID
For 56% of participants who had pathology reports available, there was 100% agreement between that report and reports from both physician and patient.
There was high agreement between patient and physician reports for the subtype of EGID, history of upper endoscopy, food impaction, esophageal dilation, and colonoscopy.

“Validation of the CEGIR Contact Registry data is important because it supports the high level of accuracy of patient-reported data in this cohort,” said lead study author Dr. Girish Hiremath, of Vanderbilt University Medical Center in Nashville, TN. “This in turn strengthens the credibility of self-reported data in this registry, which may be used for future research to help us to better understand EGIDs.”

Molecular, endoscopic, histologic, and circulating biomarker-based diagnosis of eosinophilic gastritis: Multi-site study
J Allergy Clin Immunol. Jan. 2020 Volume 145, Issue 1, Pages 255–269

This paper describes new testing platforms for blood and tissue that may help guide clinicians to a diagnosis of eosinophilic gastritis (EG) in the future. Currently, there are no consensus guidelines to standardize diagnostic criteria for EG. This is in large part due to EG being a rare condition, which makes it challenging to study, and also because it is common for people who have EG to also have another subset of eosinophilic gastrointestinal disease. The samples analyzed by the CEGIR investigators enabled them to develop a molecular profile that correlated with findings from endoscopy and histology. Levels of eotaxin-3 in the blood were strongly associated with expression of gastric cytokine CCL26. Additional studies are needed to validate these findings before these new testing platforms could be considered for clinical use.

Advancing patient care through the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR)
J Allergy Clin Immunol. Jan. 2020 Volume 145, Issue 1, Pages 28-37

In this rostum, investigators from CEGIR outline the progress and direction of the consortium and the multidisciplinary relationships and engagement with patient advocacy groups like APFED, the National Institutes of Health and partners from industry and academia. The article outlines CEGIRs work with eosinophilic gastrointestinal diseases, including natural history studies to promote clinical trial readiness tools, clinical trials, investigator training program, and innovative pilot studies.

Eosinophilic gastrointestinal disease below the belt
J Allergy Clin Immunol. January 2020 Volume 145, Issue 1, Pages 87–89

This article from the Journal of Allergy and Clinical Immunology reviews the current state of eosinophilic gastrointestinal diseases (EGIDs) with a focus on “unmet needs, barriers, and future directions in patients with nonesophageal EGIDs.” While eosinophilic esophagitis (EoE) has been the subject of much focus and advancement, EGIDs that affect other parts of the gastrointestinal tract, including eosinophilic gastritis (EG), eosinophilic gastroenteritis (EGE), and eosinophilic colitis (EC), are poorly understood by comparison and there are no well-established guidelines for diagnosis or management.

The article concludes that: 1. Clear diagnostic criteria for EG, EGE, and EC must be established; 2. outcome measures, such as patient-reported outcomes and endoscopic and histologic assessments, need to be developed; 3. More work is required to understand pathogenesis; and 4. Longitudinal trials are needed to better understand disease mechanisms and long-term outcomes.

Emerging therapies for eosinophilic esophagitis
J Allergy Clin Immunol. January 2020 Volume 145, Issue 1, Pages 38–45

This article published in the Journal of Allergy and Clinical Immunology discusses recent advances in the treatment of eosinophilic esophagitis (EoE), specifically swallowed topical steroids, biological agents, dietary approaches, and novel molecular targets. It concludes that newer formulations of swallowed topical corticosteroids have appeared to be highly effective in short- and long-term EoE management of EoE. Dietary approaches have shown a similar effectiveness; however, new approaches, such as the 2-4-6-food elimination diet (step-up approach) are similarly effective to empiric food elimination but also more efficient.

For patients who do not achieve/maintain long-term remission with steroid formulations and dietary restrictions, biological agents may be an effective treatment alternative, with anti–IL-13 and anti–IL-4 receptor antibodies thus far offering promising results in phase 2 clinical trials. The article also highlights newer targets now being tested in clinical trials, including the angiotensin II receptor type 1 (losartan) or Siglec-8 (anti–Siglec-8).

Diagnosis and treatment of eosinophilic esophagitis
J Allergy Clin Immunol. January 2020 Volume 145, Issue 1, Pages 1–7

This review from the Journal of Allergy and Clinical Immunology highlights the most recent diagnostic criteria and disease management for adult and pediatric EoE patients. The review concludes that when untreated, EoE can lead to esophageal remodeling and strictures; therefore, maintenance therapy is advised. The review also concludes that both dietary and medical therapy for EoE can help “reduce histologic inflammation, improve clinical symptoms and endoscopic abnormalities, and improve remodeling in a subset of patients.”

The authors also note the need for better ways to identify food triggers in patients with EoE, the need to identify clinical or genetic predictors of response to treat or slow progression of the disease, and the importance of identifying effective maintenance therapies.

CEGIR 2019 Publication Highlights

Association Between Endoscopic and Histologic Findings in a Multicenter Retrospective Cohort of Patients with Non-esophageal Eosinophilic Gastrointestinal Disorders.

Dig Dis Sci. 2019 Nov 26. doi: 10.1007/s10620-019-05961-4.

CEGIR researchers set out to characterize the endoscopic and histologic findings in children and adults with eosinophilic gastritis (EG), eosinophilic gastroenteritis (EGE), and eosinophilic colitis (EC) at the time of diagnosis and 6 months after the start of therapy.

“Of the 29% of subjects with post-treatment follow-up, most had an improvement in clinical, endoscopic, and histologic findings regardless of treatment utilized,” the authors noted. “Reductions in tissue eosinophilia correlated with improvements in clinical symptoms as well as endoscopic and histologic findings.”

Investigators concluded that the most common endoscopic finding was a normal appearance, which underscores the importance of biopsy even if the tissue appears visually normal during endoscopy.

“Decreased tissue eosinophilia was associated with improvement in symptoms, endoscopic, and histologic findings, showing that disease activity is reversible,” they also concluded.

Molecular, Endoscopic, Histologic and Circulating Biomarker-Based Diagnosis of Eosinophilic Gastritis: Multi-Site Study.

J Allergy Clin Immunol. 2019 Nov 15. pii: S0091-6749(19)31519-2. doi: 10.1016/j.jaci.2019.11.007.

In this publication, researchers describe their methodology and results of their work to develop tissue- and blood-based diagnostic platforms for eosinophilic gastritis EG.

“We developed tissue- and blood-based platforms for assessment of EG and uncovered robust associations between specific gastric molecular profiles and histologic and endoscopic features, providing insight and tools for this emerging rare disease,” they concluded.

Increasing Rates of Diagnosis, Substantial Co-Occurrence, and Variable Treatment Patterns of Eosinophilic Gastritis, Gastroenteritis, and Colitis Based on 10-Year Data Across a Multicenter Consortium.

Am J Gastroenterol. 2019 Jun;114(6):984-994. doi: 10.14309/ajg.0000000000000228.

In this retrospective study, researchers aimed to characterize rates of diagnosis, clinical features, and initial treatments for patients with eosinophilic gastritis (EG), eosinophilic gastroenteritis (EGE), and eosinophilic colitis (EC)

Investigators analyzed data from six centers in the Consortium of Eosinophilic Gastrointestinal Researchers from 2005-2016. In addition to demographics, time trends in diagnosis, medical history, presenting symptoms, disease overlap, and initial treatment patterns/responses were analyzed.

Some of the highlights of their findings include:

Rates of diagnosis of all diseases increased over time.

The majority of subjects had allergic conditions.

- - Presenting symptoms were similar between the diseases. The most common symptoms noted were nausea/vomiting and abdominal pain.
  - 41% of the patients in this cohort had eosinophilic inflammation outside of their primary disease location. Children more commonly had multi-site inflammation (68% vs 37%).
  - Initial treatment strategies varied greatly between centers.
  - Twenty-nine percent of the patients had follow-up within 6 months, and the majority had clinical, endoscopic, and histologic improvements.

The authors noted in their conclusion, “Future investigation should assess the cause of the increased prevalence of eosinophilic GI disorders and prospectively assess outcomes to establish treatment algorithms.”

Consortium of Eosinophilic Gastrointestinal Disease Researchers: Advancing the Field of Eosinophilic GI Disorders Through Collaboration.
Gastroenterology, March 2019;156:838–842

Dr. Sandeep Gupta, et al. published an article in the journal Gastroenterology reviewing current CEGIR projects, which included updates on the OMEGA study (Outcome Measures for Eosinophilic Gastrointestinal Diseases across Ages) and the SOFEED trial (Six Food versus One Food Eosinophilic Esophagitis Elimination Diet).

The article also discusses four novel pilot studies:

- investigating the use of losartan in patients who have eosinophilic esophagitis
- elemental diets in eosinophilic gastritis patients,
- transnasal endoscopies for monitoring EoE,
- and gaining further knowledge of the microbiome found in eosinophilic gastrointestinal disorders (EGIDs).

Other CEGIR Journal Publications

https://www.rarediseasesnetwork.org/cms/Portals/8/Docs/CEGIR%20Publications%2020160830.pdf